Liquid biopsy to detect resistance mutations against anti-epidermal growth factor receptor therapy in metastatic colorectal cancer

Abstract

Colorectal cancer (CRC) is a major cause of mortality worldwide, associated with a steadily growing prevalence. Notably, the identification of KRAS, NRAS, and BRAF mutations has markedly improved targeted CRC therapy by affording treatments directed against the epidermal growth factor receptor (EGFR) and other anti-angiogenic therapies. However, the survival benefit conferred by these therapies remains variable and difficult to predict, owing to the high level of molecular heterogeneity among patients with CRC. Although classification into consensus molecular subtypes could optimize response prediction to targeted therapies, the acquisition of resistance mutations to targeted therapy is, in part, responsible for the lack of response in some patients. However, the acquisition of such mutations can induce challenges in clinical practice. The utility of liquid biopsy to detect resistance mutations against anti-EGFR therapy has recently been described. This approach may constitute a new standard in the decision algorithm for targeted CRC therapy.

Keywords: Colorectal neoplasms; Precision medicine; Liquid biopsy; Cetuximab; Panitumumab

Core Tip: Contemporary management of metastatic colorectal cancer patients with wild type KRAS includes the use of anti-epidermal growth factor receptor (EGFR) agents, such as cetuximab or panitumumab, as first-line treatment. However, a significant number of patients receiving this treatment show disease progression. Some of the relapses could be explained by the presence of acquired resistance mutations in KRAS. Liquid biopsy of circulating tumor cells or circulating cell-free DNA is expected to improve the management of patients undergoing anti-EGFR therapy.